Neurotrophic factors are believed to be elaborated by target tissues, taken up into nerve terminals, and then transported retrogradely to neuronal cell bodies. Neurons are dependent on neurotrophic factors (NTF's) for survival and/or function, and many NTF's are thought to exist, each directed against a specific neuronal type or several types. While the NTF's are usually produced in extraordinarily small quantities by target tissues, several putative NTF's have been at least partially purified and shown to possess survival-promoting leffects in vitro.
The survival of the neurons is essential for the maintenance of normal target organ function. In a number of conditions where nerves are damaged or destroyed, the target organ atrophies or exhibits abnormal functions. Hence, the use of NTF's should not only promote neuronal survival but also maintain normal target organ function.
A mutually beneficial, reciprocal relationship exists between the target tissue and neuron. While the target tissue supplies NTF's for neurons, the neurons also provide trophic support and regulate the function of the target tissue. Indeed, in many cases and in clinical disorders, when the neurons die there is atrophy and loss of function of the target tissue. Thus, exogenously applied NTF's not only would directly support the survival and function of neurons, but also indirectly benefically support or alter the function of the target tissue.
There are ocular diseases that may benefit from the activities of NTF's. For example, glaucoma is a disease characterized by an increase in intraocular pressure, cupping of the optic nerve head, and loss of visual field. Insufficient cholinergic innervation of the ciliary muscle in the eye may contribute to the decreased outflow of aqueous humor resulting in elevated intraocular pressure. At the present time, the condition is treated with anticholinesterases and parasympathomimetics. Therefore, enhancement of endogenous cholinergic tone by NTF's could be an effective therapy. Cholinergic innervation of the ciliary muscle originates in the ciliary ganglion. Stimulation of acetylcholine (muscarinic) receptors results in contraction of the ciliary muscle, decreased outflow resistance, and decreased intraocular pressure. Thus if NTF's could be used to stimulate acetylcholine receptors indirectly, for example by enhancing production of acetylcholine, the ciliary muscle would contract more forcefully, thereby enhancing outflow. Other diseases of the eye which may benefit from enhanced activation of the parasympathetic nerves by treatment with NTF include Adie's syndrome, dry eye, presbyopia, disorders of lacrimation, corneal wound disorders, and the like.
In view of the fact that there seem to be a large number of different neurotrophic growth factors, which appear to have different characteristics and different properties somewhat analogous to the sequence of interleukins, it is of great interest to be able to identify all of the naturally occurring NTF's, characterize them as to their physiological activities, either individually or in combination, and determine their utility in treating a wide variety of symptoms, syndromes, and diseases.